Double-stranded RNA and bacterial lipopolysaccharide enhance sensitivity to TNF-alpha-mediated cell death.
The effect of double-stranded RNA (dsRNA) and bacterial lipopolysaccharide on the sensitivity to tumor necrosis factor (TNF)-alpha-mediated cell death was studied in an in vitro system. Since secretion of TNF-alpha is a part of the early host response to viral and bacterial infection, we examined whether mimicking the infection with viral and bacterial products could affect the response of cells to TNF-alpha. Incubation of WEHI 164 fibrosarcoma cells with dsRNA or lipopolysaccharide (LPS) significantly increased their sensitivity to TNF-alpha-mediated lysis and to TNF-secreting inflammatory T cell-mediated lysis. Thus, these products could induce increased sensitivity to TNF-alpha in cells in an inflammatory focus, possibly contributing to selective elimination of infected but not healthy cells by this non-specific cytokine. Additionally, our data show that both dsRNA and LPS, as well as TNF-alpha itself, rapidly induce nuclear factor-kappa B (NF-kappa B), a DNA-binding protein implicated in regulation of gene expression. We suggest that NF-kappa B could regulate genes crucial for the induction of cell death by TNF-alpha.
Gromkowski
S H
SH
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510.
Mama
K
K
Yagi
J
J
Sen
R
R
Rath
S
S
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000096:biosynthesis; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D014409:Tumor Necrosis Factor-alpha; D011070:Poly I-C